title: Ionic liquids in drug delivery.
abstract: BACKGROUND
  To overcome potential problems with solid-state APIs, such as polymorphism, solubility and bioavailability, pure liquid salt (ionic liquid) forms of active pharmaceutical ingredients (API-ILs) are considered here as a design strategy.
  
  
  METHODS
  After a critical review of the current literature, the recent development of the API-ILs strategy is presented, with a particular focus on the liquefaction of drugs. A variety of IL tools for control over the liquid salt state of matter are discussed including choice of counterion to produce an IL from a given API; the concept of oligomeric ions that enables liquefaction of solid ILs by changing the stoichiometry or complexity of the ions; formation of 'liquid co-crystals' where hydrogen bonding is the driving force in the liquefaction of a neutral acid-base complex; combining an IL strategy with the prodrug strategy to improve the delivery of solid APIs; using ILs as delivery agents via trapping a drug in a micelle and finally ILs designed with tunable hydrophilic-lipophilic balance that matches the structural requirements needed to solubilize poorly water-soluble APIs.
  
  
  CONCLUSIONS
  The authors believe that API-IL approaches may save failed lead candidates, extend the patent life of current APIs, lead to new delivery options or even new pharmaceutical action. They encourage the pharmaceutical industry to invest more research into the API-IL platform as it could lead to fast-tracked approval based on similarities to the APIs already approved.
authors.affiliation: The University of Alabama, Center for Green Manufacturing and Department of Chemistry , Tuscaloosa, AL , USA rdrogers@as.ua.edu.
authors.forename: Julia L
authors.initials: JL
authors.lastname: Shamshina
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Barber
authors.forename: Robin D
authors.initials: RD
authors.lastname: Rogers
mesh_terms: D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D016503:Drug Delivery Systems; D004345:Drug Industry; D057927:Hydrophobic and Hydrophilic Interactions; D052578:Ionic Liquids / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000008:administration & dosage; D012492:Salts / Q000008:administration & dosage; D012995:Solubility
chemical_list: D052578:Ionic Liquids; D004364:Pharmaceutical Preparations; D012492:Salts